(Philadelphia, PA) - Researchers at the University of Pennsylvania
School of Medicine found that chronic ibuprofen therapy given
after brain injury worsens cognitive abilities. These findings - in a
preliminary, animal-model study - have important implications for traumatic
brain injury (TBI) patients who are often prescribed such nonsteroidal
anti-inflammatory drugs (NSAIDS) as ibuprofen for chronic pain. The findings
appear online this month in Experimental Neurology.

Because several studies in animals and humans have shown that long-term
use of ibuprofen for inflammation improves outcome for Alzheimer’s
patients by reducing symptoms and delaying the onset of dementia, the
researchers investigated whether ibuprofen improved long-term cognitive
outcome in brain-injured animals.

Over four months, rats received ibuprofen in their food proportional to
doses given to humans. In the two groups of injured rats (one fed ibuprofen
and the other not), there was a significant overall deficit in the animals’
ability to find an underwater platform in a Morris water maze, a common
test used to assess cognitive ability in animals.

“But to our surprise, we found that the injured rats given ibuprofen
were far worse compared to the injured rats that had no treatment at all,”
says lead author Douglas H. Smith, MD, Director of the
Center for Brain Injury and Repair. “Although most untreated injured
animals could find the platform, they were much slower to learn its location
than non-injured animals. In contrast, almost none of the treated, injured
animals could find the platform at all.”

However, there were no outward signs of difference in the extent of atrophy
in the hippocampus or cortex of treated versus non-treated injured rats.
Although ibuprofen treatment did reduce chronic inflammatory changes in
the brains of injured animals, that did not seem to have an influence
over the extent of damage to the brain regions associated with learning
and memory.

This initial study demonstrates that the effects of long-term treatment
with NSAIDS like ibuprofen after a head injury are poorly understood.
“We have to remember these are animal studies, and what we can take
home is that we need further examination of potential negative effects
in patients,” says Smith. “I hope these findings inspire studies
in patients to evaluate the safety, efficacy, and potential long-term
problems with cognition of chronic ibuprofen use in TBI patients.”

In Alzheimer’s patients, chronic ibuprofen appears to be beneficial
by delaying onset and severity of symptoms. Similarly, chronic ibuprofen
therapy in a mouse model of Alzheimer’s disease reduces plaque build-up
in the brain and improves function. However, finding that this same approach
to treatment worsens the outcome in an animal model of TBI may have important
implications for TBI patients who are often prescribed NSAIDS for chronic
pain. With few alternative over-the-counter pain medicines available to
these patients, further investigation is essential, says Smith.

Study co-authors are Kevin D. Browne, Akira Iwata, and M.E. Putt, all
from Penn. The research was supported by grants from the National Institutes
of Health.

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